Journal of

Clinical Medicine

Article
The Role of Diffusion-Weighted Magnetic Resonance
Imaging in the Differentiation of Head and
Neck Masses
Lutfi Kanmaz 1 and Erdal Karavas 2, * ID

1 Department of Otorhinolaryngology—Head and Neck Surgery, Pazarcık State Hospital,

Kahramanmaraş 46700, Turkey; lutfikanmaz@gmail.com
2 Department of Radiology, Faculty of Medicine, Erzincan University, Erzincan 24100, Turkey
* Correspondence: erdalkaravas@hotmail.com; Tel.: +90-446-212-2222




Received: 22 April 2018; Accepted: 21 May 2018; Published: 29 May 2018


Abstract: The purpose of this study was to evaluate the value of diffusion-weighted MRI (DW-MRI)
in differentiating benign and malignant head and neck masses by comparing their apparent diffusion
coefficient (ADC) values. The study included 32 patients with a neck mass >1 cm in diameter who
were examined with echo planar DW-MRI. Two different diffusion gradients (b values of b = 0 and
b = 1000 s/mm2 ) were applied. DWI and ADC maps of 32 neck masses in 32 patients were obtained.
Mean ADC values of benign and malignant neck lesions were measured and compared statistically.
A total of 15 (46.9%) malignant masses and 17 (53.1%) benign masses were determined. Of all
the neck masses, the ADC value of cystic masses was the highest and that of lymphomas was the
lowest. The mean ADC values of benign and malignant neck masses were 1.57 × 10−3 mm2 /s and
0.90 × 10−3 mm2 /s, respectively. The difference between mean ADC values of benign and malignant
neck masses was significant (p < 0.01). Diffusion-weighted MRI with ADC measurements can be
useful in the differential diagnosis of neck masses.

Keywords: neck mass; diffusion-weighted MRI; apparent diffusion coefficient

1. Introduction
Quick and accurate diagnosis directly affects treatment success for patients with a neck mass,
which is a common finding in ENT clinics. Inadequate or late diagnosis of a malignant mass increases
the morbidity and mortality of a disease.
The rapid development of diagnostic imaging technology has provided clinical practice with
new facilities for the evaluation of neck masses. These new methods are gaining importance with the
advantageous factors of cost and ease of use. At present, ultrasonography (USG) and/or computed
tomography (CT) are used as conventional methods for the evaluation of neck lesions.
If necessary, magnetic resonance imaging (MRI) is used for the characterization of neck masses.
MRI evaluates the morphology, signal intensity and enhancement pattern of lesions. However, none of
these methods can accurately differentiate benign from malignant lesions. This has led to the necessity
of researching new diagnostic methods. Diffusion-weighted magnetic resonance imaging (DW-MRI) is
a non-contrast enhanced technique that can be obtained during a single breath-hold. In the literature,
DW-MRI was first used in the early diagnosis of stroke in neuroradiology [1,2]. In the early period,
the use of this technique was limited in the central nervous system due to its sensitivity to cardiac,
respiratory, and peristaltic movements. However, following improvements in the echo planar imaging
technique as a fast MRI sequence, it became possible to successfully apply diffusion-weighted echo
planar MRI even in other areas with high-susceptibility artifacts. DW-MRI was first applied to head

J. Clin. Med. 2018, 7, 130; doi:10.3390/jcm7060130 www.mdpi.com/journal/jcm

J. Clin. Med. 2018, 7, 130 2 of 10

and neck lesions in 2001 and promising results have been achieved [3]. Subsequent studies showed that
DW-MRI appeared to be helpful in differentiating epidermoid carcinoma and malignant lymphoma,
staging neck nodal disease, and distinguishing radiotherapy-induced tissue changes from persistent
or recurrent cancer. In these studies, apparent diffusion coefficient (ADC) values of tissues and lesions
are calculated using diffusion-weighted images and different values in the differential diagnosis.
Moreover, with the use of this imaging technique, the creation of an ADC map is an excellent method
for differentiation between the viable and necrotic parts of head and neck tumors. Thus, the ADC map
can be used to select the best biopsy site and to detect tumor viability in the post-treatment follow-up
of patients after radiation therapy. The technique may also be useful in characterizing thyroid nodules
and salivary gland neoplasms.
The purpose of this study was to evaluate the value of DW-MRI in differentiating benign and
malignant head and neck masses by comparing their ADC values.

2. Materials and Methods

This prospective study was performed on 43 consecutive patients who underwent MRI for a
diagnosis of head and neck lesions in our center. All patients were examined with contrast-enhanced
MRI and DW-MRI. The study was conducted in the Department of Otorhinolaryngology, Bakırköy Dr.
Sadi Konuk Training and Research Hospital, in the period of June 2009 to June 2010.
Institutional Ethics Committee approval was obtained for the study.

2.1. Subjects
A total of 11 patients were excluded from the study; four patients with neck masses <1 cm in the
greatest minimal transverse diameter, two who had undergone biopsy, three due to distortion artifacts,
and two with a final diagnosis of neck metastasis of a thyroid carcinoma.
Thus the final study population of 32 consecutive patients with neck masses >1 cm in diameter
consisted of 12 females (37.5%) and 20 males (62.5%) with a mean age of 45.13 ± 17.08 years (range,
9–78 years). All patients were questioned in detail about age, location, and duration of the mass,
associated symptoms, and then routine blood tests such as serological tests were applied. Within the
head and neck examination, diagnostic pan-endoscopy of the nasal cavity, nasopharynx, oropharynx,
hypopharynx, and larynx was also performed. All clinical evaluations were documented.
When patients had multiple neck masses with the same histological diagnosis, only the largest
one was used for calculation of ADC values. Thus, the diffusion-weighted images and ADC maps of
32 neck masses in 32 patients were studied.
Localization of the lesions was classified according to the lymph node regions and neck
facial spaces. The final diagnosis of the patients was made by histopathological examination of
surgical specimens. A diagnosis of tuberculosis lymphadenitis was made by histology and culture,
two undifferentiated nasopharyngeal carcinoma metastases by primary tumor biopsy and FNAB,
neck metastasis in five patients with NHL diagnosed by excisional lymph node biopsy, and one
adenocarcinoma metastasis by FNAB. A diagnosis of SCC metastasis was confirmed with neck
dissection. Diagnosis of carotid body paraganglioma in one patient was established with MR
angiography and DSA (digital subtraction angiography) before excision.

2.2. MR Imaging Techniques

All the MR examinations were performed with a 1.5 Tesla MR unit (Siemens Avanto, Erlangen,
Germany). Routine examination consisted of T2-weighted fast spin-echo images (with a section
thickness of 4 mm, an interslice gap of 1–2 mm, a field of view (FOV) of 25–30 cm and an acquisition
matrix of 256 × 224) and DW-MRIs. Before DW-MRI, T2-weighted images were obtained in the axial
plane. A total of 14 transverse images covering the lesions were obtained. DW-MRIs were obtained at
the section level where the largest transverse section of the lesion was detected on the MRIs which
were obtained before administration of contrast material. DW-MRI was obtained using multi-slice
J. Clin. Med. 2018, 7, 130 3 of 10

spin-echo single-shot echo planar imaging in the axial plane. For each patient, diffusion-weighted
images and ADC maps were obtained by applying diffusion-sensitive gradients in three orthogonal
directions (x, y, and z) and two different b-values (0 and 1000 s/mm2 ). ADC maps of the images were
automatically reconstructed on the main console. Then, the region of interest (ROI) was defined by a
radiologist measuring the signal intensity of the lesion. ROIs were determined on the solid appearing
parts for the solid masses and on the cystic areas for the cystic lesions. The ADC values of the lesions
were calculated with an ROI >1 cm2 .

2.3. Statistical Analysis

Statistical analyses of the study data were performed using NCSS (Number Cruncher Statistical
System) 2007 and PASS (Power Analysis and Sample Size) 2008 Statistical Software (HyLown
Consulting LLC., Atlanta, GA, USA). The Student’s t-test was used to compare data between two
groups. Results were stated as the mean and standard deviation. Qualitative data were compared
using the chi-square test. The receiver operating characteristic (ROC) curve was applied to determine
the cut-off point with the highest accuracy and sensitivity. The value of p < 0.05 was considered
statistically significant at a 95% confidence level.

3. Results
This study was performed on 32 consecutive patients with head and neck masses who underwent
echo planar DW-MRI from June 2009 to June 2010. The patients consisted of 12 females (37.5%) and
20 males (62.5%) with a mean age of 45.13 ± 17.08 years (range, 9–78 years).
Malignant masses were determined in 15 (46.9%) cases and benign masses in 17 (53.1%).
The benign masses consisted of five pleomorphic adenoma originating from major salivary glands,
three reactive lymphadenopathies, two branchial cleft cysts, two cervical sympathetic chain
schwannomas, two Whartin’s tumors, one glomus tumor, one tbc lymphadenitis, and one thyroglossal
duct cyst. The malignant masses were five Non-Hodgkin’s lymphoma, three larynx SCC met., two
undifferentiated carcinoma met., two oropharynx SCC met., one GIS adeno ca met., one primary
unknown carcinoma met., and one tonsil SCC met. The diagnoses of the patients are listed in Table 1.
Of the total neck masses, the ADC value of cystic masses was the highest (1.98 × 10−3 mm2 /s)
and that of lymphomas (0.80 × 10−3 mm2 /s) was the lowest. The mean ADC values of benign and
malignant neck masses were 1.57 × 10−3 mm2 /s and 0.90 × 10−3 mm2 /s, respectively. The difference
between the mean ADC value of benign and malignant neck masses was statistically significant
(p < 0.01). The localizations of the masses are listed in Table 1. The numbers of malignant and benign
masses were 15 (46.9%) and 17 (53.1%), respectively. The mean ADC value of benign masses with
high signal intensity was statistically significantly higher than that of malignant masses with low
signal intensity (p < 0.01) (Table 2). Malignant masses were classified in two categories as malignant
lymphomas (33.3%) and carcinomas (66.7%, squamous cell carcinoma or adenocarcinoma). There was
no statistically significant difference between the two categories in the malignant group (p > 0.05)
(Table 2). When an ADC value of 1.13 × 10−3 mm2 /s or less was used to predict malignancy, the best
results were achieved with high accuracy, with sensitivity of 93.33%, specificity of 82.35%, positive
predictive value of 82.35%, and a negative predictive value of 93.33% (Table 3).
The ROC curve was used to evaluate the diagnostic capability of the ADC value to differentiate
benign from malignant masses. When 1.13 × 10−3 mm2 /s was used as a threshold value in
differentiating benign from malignant masses, the area under the curve was 0.918 (Table 4, Figure 1).
J. Clin. Med. 2018, 7, 130 4 of 10

Table 1. Diagnosis and localization of 32 head and neck masses.

Diagnosis n %
Pleomorphic adenoma 5 15.6
Reactive lymphadenitis 3 9.4
Branchial cleft cyst 2 6.3
Schwannoma 2 6.3
Whartin tumor 2 6.3
Glomus tumor 1 3.1
Tbc lymphadenitis 1 3.1
Thyroglossal duct cyst 1 3.1
Non-hodgkin’s lymphoma 5 15.6
Larynx SCC metastasis 3 9.4
Undifferentiated carcinoma metastasis 2 6.3
Oropharynx SCC metastasis 2 6.3
GIS adenocarcinoma metastasis 1 3.1
Primary unknown carcinoma met. 1 3.1
Tonsil SCC metastasis 1 3.1
Localizations n %
Anterior cervical 1 3.1
Superior lateral cervical 9 28.1
Middle lateral cervical 3 9.4
Posterior cervical 1 3.1
Sup-mid lateral cervical 2 6.3
Parapharyngeal area 3 9.4
Parotid area 7 21.9
Submandibular area 5 15.6
Supraclavicular area 1 3.1

Table 2. Pathological diagnosis and distribution of mean ADC values in the examined groups.

Pathology n % ADC (×10−3 mm2 /s) Ave. ± SD. +p

Malignant 15 46.9 0.90 ± 0.17
0.001 **
Benign 17 53.1 1.57 ± 0.42
Lymphoma 5 33.3 0.80 ± 0.14
0.100
Carcinoma 10 66.7 0.96 ± 0.17
+ Student t test; ** p ≤ 0.001.

Table 3. Calculating the threshold value.

Value Sensitivity Specificity Positive Predictive Value Negative Predictive Value Accuracy Relative Risk
0.95 66.67 88.24 83.33 75.00 78.13 3.33
0.98 66.67 82.35 76.92 73.68 75.00 2.92
1.05 80.00 82.35 80.00 82.35 81.25 4.53
1.12 86.67 82.35 81.25 87.50 84.38 6.50
1.13 93.33 82.35 82.35 93.33 87.50 12.35
1.20 100.00 82.35 83.33 100.00 90.63 -
1.21 100.00 76.47 78.95 100.00 87.50 -
1.34 100.00 70.59 75.00 100.00 84.38 -

Table 4. Area under the curve (AUC).

Area under the Curve

p 95% Confidence Interval

Area Std. Error (a)
Upper Lower
0.918 0.05 0.001 0.819 1.016
J. Clin. Med. 2018, 7, 130 5 of 10
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Figure1.1.Receiver
Figure Receiveroperating
operatingcharacteristic
characteristic(ROC)
(ROC)curve
curveofofthe
theADC
ADCvalue.
value.

4.4.Discussion
Discussion
Diffusion
Diffusionisisdefined
definedasasthe therandomized
randomizedmicroscopic
microscopicmovement
movementofofwater watermolecules
moleculesand andisisused
used
asasa asensitive
sensitiveparameter
parameterfor forthe thecharacterization
characterizationofoftissue tissueatata amicroscopic
microscopiclevel. level. Today,
Today,ininvivo vivo
measurement
measurementofofdiffusion diffusionisispossible
possiblewith
withDW-MRI
DW-MRIand andADC ADCmeasurements.
measurements.As Asa aresult
resultofofnewnew
technological
technologicaldevelopments,
developments, MRIMRI has become
has become sensitive to the diffusion
sensitive of water protons
to the diffusion of water in biological
protons in
tissues and diffusion-weighted
biological tissues and diffusion-weightedimaging can be obtained.
imaging canIntracellular
be obtained. and extracellular
Intracellular andwater balance
extracellular
iswater balance is also shown in a way that is important for diagnosis and follow-up of use
also shown in a way that is important for diagnosis and follow-up of stroke. Initially, the stroke.
of
this technique
Initially, the wasuse limited
of this to brain studies
technique was because
limited of to technical
brain studiesproblems regarding
because motionproblems
of technical artifact
due to cardiac,
regarding respiratory,
motion artifactand dueperistaltic movements.
to cardiac, However,
respiratory, following improvements
and peristaltic movements. However, in echo
planar imaging
following techniques, an
improvements in echo planar DW-MRI can now be successfully
imaging techniques, an echo planar performed
DW-MRI evencaninnow
areasbe
successfully
with performedartifacts
high susceptibility even in[4]. areas
Thiswith high susceptibility
technique was first used artifacts [4]. This technique
in neuroradiological was for
imaging first
used in of
diagnosis neuroradiological
early cerebral ischemia imaging andforhasdiagnosis
become aof early cerebral
diagnostic ischemia
tool in this and has become a
area [1,5].
In 1994,tool
diagnostic Muller et al.area
in this measured
[1,5]. the ADC of water in liver, spleen, kidney, and muscle and showed
that inIn 1994,
vivo Mullermeasurements
diffusion et al. measured of the ADC oforgans
abdominal water obtained
in liver, spleen,
with MRI kidney,
couldandprove muscle
helpfuland
inshowed that in vivoand
the identification diffusion measurements
classification of abdominalof abdominal
disease organs obtained with
[6]. Subsequently, in MRI
severalcould prove
studies,
helpful in
DW-MRI hasthe beenidentification
shown to be and classification
able to be used in of the
abdominal
differentialdisease [6]. Subsequently,
diagnosis of lesions in the in several
liver,
kidney,
studies, and other abdominal
DW-MRI has been shown organs to with
be the
ablemeasurement
to be used inof theADCs [7,8]. diagnosis of lesions in the
differential
liver,
In kidney, and other
the literature, DW-MRIabdominalhas alsoorgans
beenwithseen the measurement
to have an applicationof ADCsarea[7,8].
in the different regions
of the In theand
head literature,
neck. TheDW-MRI has also been
characterization of seen
headtoandhave an application
neck lesions witharea echoinplanar
the different
DW-MRI regions
by
of theethead
Wang al. [3]andwasneck. The study
the first characterization
in this area.ofThey
head found
and neck thatlesions
the mean with ADCechovalue
planarof DW-MRI
the benignby
Wangwas
lesions et al.statistically
[3] was thesignificantly
first study in this area.
different thanThey
thatfound that the lesions.
of malignant mean ADC value
In 2003, Sumiof the benign
et al. [9]
lesionsthe
studied wasdifferential
statisticallydiagnosis
significantly different lymph
of metastatic than that of malignant
nodes lesions. In 2003, MR
with diffusion-weighted Sumi et al. [9]
imaging.
studied
Over theyears,
several differential
furtherdiagnosis
studies have of metastatic
been madelymph in thisnodes
area. Inwith diffusion-weighted
another study on neck lymph MR imaging.
nodes,
Overmaps,
ADC several as years,
a new further
technique, studies
havehave
beenbeenusedmade in this area.
to determine the In another
necrotic and study on neck lymph
non-necrotic solid
nodes,
areas ADC maps,
of malignant as a new
lesions [10].technique,
Eida et al.have been used
[11] reported to determine
that preoperative thetissue
necrotic and non-necrotic
characterization of
solid areas
salivary of malignant
gland tumors could be made lesionswith[10].
ADC Eida
map et al. [11] reported
construction. In anotherthat study,preoperative
Abdel Razek tissueet al.
characterization
reported that the mean of salivary
ADC value glandoftumors
malignantcould be made
thyroid withwas
nodules ADC map construction.
statistically significantlyIn another
lower
study,
than thatAbdel
of benign Razek
oneset[12].
al. The
reported thattechnique
diffusion the meaninvolves
ADC value of malignant
the diffusion motionthyroid
of waternodules
protonswas in
statistically significantly lower than that of benign ones [12]. The diffusion technique involves the
diffusion motion of water protons in the tissues. According to the diffusion of tissue, the diffusion of
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J. Clin. Med. 2018, 7, 130 6 of 10

water molecules varies in the different regions of tissue. Therefore, the diffusion coefficient of the
tissue J.varies
Clin. Med.depending on any
2018, 7, x FOR PEER REVIEWchange in the proportion of extracellular to intracellular 6 of 10 water
the tissues. According to the diffusion of tissue, the diffusion of water molecules varies in the different
molecules. Thus, diffusion-weighted MR imaging produces different contrast and ADC values
regions of tissue. Therefore, the diffusion coefficient of the tissue varies depending on any change in
water
according molecules varies in the different regions of tissue. Therefore, the diffusion coefficient of the
theto the microstructure
proportion of extracellularoftothe tissues
intracellular [3].
water molecules. Thus, diffusion-weighted MR imaging
Intissue
the varies depending on any change in the proportion of extracellular to intracellular water
current
produces study,
different the and
contrast meanADC ADC value
values of benign
according masses with
to the microstructure high
of the signal
tissues [3]. intensity was
molecules. Thus, diffusion-weighted MR imaging produces different contrast and ADC values
significantly In the
(Figurecurrent study,
2) higher than the mean ADC value
thattissues
of malignantof benign masses with high signal
(Figure 3) masses with low signal intensity wasintensity.
according to the microstructure of the [3].
significantly (Figure 2) higher than that of malignant (Figure 3) masses with low signal intensity. These
These differences in ADC values
In the current mayADC be value
explained by the differences
with high in the intensity
histopathological
differences in ADC study,
values maythe mean
be explained of benign
by the differences masses
in signal
the histopathological characteristics was
of
characteristics
significantly of benign
benign and (Figure
malignant
and malignant
2) tumors.
higher than tumors.
that of
Generally,
Generally,
malignant
malignant
malignant
(Figure
tumors
tumors
show3)hypercellularity
masses with low show
and signal
hypercellularity
intensity.
have enlarged
and have nuclei, and hyperchromatism. These histopathological characteristics reduce the diffusion spacereduce
These enlarged nuclei,
differences in and
ADC hyperchromatism.
values may be These
explained byhistopathological
the differences in characteristics
the histopathological
of the
characteristics
diffusion space
water protonsofinbenign
of water and malignant
theprotons in the
extracellular tumors. Generally,
andextracellular
intracellular malignant tumors
and intracellular
regions [13,14]. regionsshow hypercellularity
[13,14].
and have enlarged nuclei, and hyperchromatism. These histopathological characteristics reduce the
diffusion space of water protons in the extracellular and intracellular regions [13,14].

FigureFigure
2.Figure
Pleomorphic
Pleomorphic
2.2.Pleomorphic adenoma
adenoma
adenoma of of
the
ofthe
theparotid
parotid gland.
parotid gland.
gland. (a)(a)Axial
(a) Axial
Axial T2-weighted
T2-weighted
T2-weighted imageimage
image(T2WI)
(T2WI) (T2WI)
shows
showsa shows
a a
mass in theinleft
mass
mass in
the parotid
the
left gland;
leftparotid
parotid (b)(b)
gland;
gland; the
(b) lesion
the
the lesionshows
lesion shows low
shows lowsignal
low signal
signal intensity
intensity
intensityon on
onDWI;DWI;
DWI;and
and and
(c)(c) (c)mass
thethe
massthe mass is
is is
hyperintense on the ADC map (ADC value of 1.55 × 10 −3 mm2 /s).
hyperintense on the
hyperintense onADCthe ADCmap (ADC
map (ADC value
valueof
of1.55 10 mm
1.55 × 10 −3−3 mm/s).
2 2/s).

Figure
Figure3.3.Undifferentiated
Undifferentiatednasopharyngeal
nasopharyngeal carcinoma.
carcinoma. (a) (a) Axial
Axial T2WI
T2WIshows
showsbilateral
bilateral metastatic
metastatic
cervical
cervicallymph
lymphnodes;
nodes; (b) lymphnode,
(b) lymph node,onon
thethe
leftleft
sideside of neck,
of the the neck,
showsshows high signal
high signal intensityintensity
on DWI;on
FigureDWI;
3. Undifferentiated
and (c) the mass is nasopharyngeal
hypointense on the carcinoma.
ADC map (a)
(ADC Axial
value of
and (c) the mass is hypointense on the ADC map (ADC value of 0.91 × 10 mm /s). T2WI
−
0.913 × shows
102−3 mm2bilateral
/s). metastatic
cervical lymph nodes; (b) lymph node, on the left side of the neck, shows high signal intensity on
Apparently
DWI; and Apparently higher
(c) the mass
higher ADCvalues
is hypointense
ADC values onfor
for thebenign
benignADC cystic
map
cystic masses
(ADC
masses may bemay
value be expected
of 0.91
expected × 10−3 mm
because ofbecause
2/s).
the of the
relatively
relatively
freer mobility of water protons in the fluid. In the current study, cystic masses were not groupednot
freer mobility of water protons in the fluid. In the current study, cystic masses were
grouped
Apparently separately
separately due
higher due
to lowADC to low
numbers. numbers.
values for However,
However, consistent
benign consistent with studies,
with previous
cystic masses previous
may be studies,
the mean ADC
expectedthe mean
valueADC
becauseof of the
value
threeofcystic
threemasses
cystic masses
(Figure 4)(Figure
(1.98 ×4)10(1.98mm
− 3 × 10/s)mm
2 −3
was /s)
2 wasthan
higher higher
thatthan that benign
of other of other benign
solid solid
masses
relatively freer mobility of water protons in the fluid. In the current study, cystic masses were not
masses
(ADC (ADC
= 1.48 × 10−3 ×mm
= 1.48 10−32 /s).
mmIn2/s). In addition,
addition, the differences
the differences in ADC
in ADC values values
among among
cystic cystic
masses masses
could be
grouped separately
could be explained
explained
due to low
by the
by the different
numbers.
different
protein
However, consistent
protein concentrations.
concentrations.
with
A high protein levelA high
previous
protein
restricts
studies, the
level restricts
the movement
mean
of waterthe
ADC
value of three cystic
movement
molecules masses
ofbywater (Figure
molecules
increasing 4) (1.98
[15]. ×the
by increasing
the viscosity 10−3viscosity
mm2/s)[15].was higher than that of other benign solid
masses (ADC = 1.48 × 10−3 mm2/s). In addition, the differences in ADC values among cystic masses
could be explained by the different protein concentrations. A high protein level restricts the
movement of water molecules by increasing the viscosity [15].
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Figure 4. 4.
Figure Second
Secondbranchial
branchialcleft
cleftcyst.
cyst.(a)
(a)Axial
Axial T2WI
T2WI shows
shows aa unilocular
unilocularcystic
cysticmass
massinin the
the left
left carotid
carotid
Figure 4. Second branchial cleft cyst. (a) Axial T2WI shows a unilocular cystic mass in the left carotid
space; (b)
space; (b)the
thelesion
lesion shows lowsignal
shows low signalintensity
intensity
on on
DWI;DWI;
andand (c)lesion
(c) the the lesion is hyperintense
is hyperintense on the
on the ADC
space; (b) the lesion shows low signal intensity on DWI; and (c) the lesion is hyperintense on the
ADC
mapmap
(ADC (ADC value
value of 2.02 × 10−
of 2.02 ×310 −3 mm
mm 2/s).
2 /s).
ADC map (ADC value of 2.02 × 10−3 mm2/s).

Sumi
Sumi et al. [16]reported
reported that
the the mean
ADC ADC value of lymphomas is lower ofthan that of
Sumi etetal.al.[16]
[16] reportedthatthat mean
the mean value of
ADC lymphomas
value is lower is
of lymphomas than that than
lower metastatic
that of
metastatic
lymph lymph
nodes nodes of
of carcinomas carcinomas due
due to the due to the
difference difference
in cellularin in cellular
density. density. Maeda et al. [17] also
metastatic lymph nodes of carcinomas to the difference cellularMaeda
density. et Maeda
al. [17] etalsoal.reported
[17] also
reported
that
reported that
carcinomascarcinomas
that carcinomas could
could contain contain
couldsmall
containfocismall foci
foci of
of necrosis
small necrosis
of on onhistopathological
histopathological
histopathological
necrosis on examination examination
that was that
examination that
not
was not identifiable
identifiable on conventional
on conventional
was not identifiable MRI. This
on conventional MRI.
MRI. This investigation
investigation has alsohas
This investigation has
beenalso been
alsoused
beentousedused
explain to explain
the higher
to explain the higher
ADC
the higher
ADCADC values of SCCs than those of lymphomas. In the current study, although there was nono
values
values of of
SCCs SCCs
than than
those those
of of
lymphomas. lymphomas.
In the In
current the current
study, study,
although although
there was no there was
statistically
statistically
significant
statisticallysignificant
significantdifference,
difference, the mean ADC
difference, the mean
thevalue
meanof ADC value
lymphomas
ADC value of of(Figure
lymphomas
lymphomas 5) (0.80 × 10−5)
(Figure
(Figure
35)
mm
(0.80
2 /s)×was
(0.80 × 1010−3 −3
mm mm
lower 2/s)
2/s)

was lower
that than thethat − 3 2
than
was lower ofthan thatofof
other the
theother
malignant malignant
othertumors
malignant(0.96 tumors
× 10 mm
tumors (0.96/s).
(0.96 ×× 10
10
In−3 mm
−3 the
mm 2 /s).InInthe
malignant
2/s). the malignant
group,
malignantlarynx group,
SCC
group,
metastasis with the value of 1.15 × 10 −3 mm2 /s showed the highest values.
larynx SCC metastasis with the value of
larynx SCC metastasis with the value of 1.15 × 10 1.15 × 10−3
−3 mm 2/s
2 showed the highest
showed the highest values. values.

Figure 5.5. Non-Hodgkin

Non-Hodgkinlymphoma.
lymphoma.(a)(a) Axial T2WI shows metastatic cervical lymph
node node nearby
Figure
Figure
SCM;
5.(b)Non-Hodgkin
the lymph
lymphoma.
node, on the
(a)Axial
right
Axial
side
T2WI
of
T2WI
the
shows
neck at
metastatic
shows level of
cervical
metastatic
lateral
lymph
cervical
cervical
lymph
region,
nearby
node SCM;
shows
nearby
high
(b) the lymph node, on the right side of the neck at level of lateral cervical region, shows high signal
SCM; (b)
signal the lymph
intensity on node,
DWI; on
and the
(c) right
the side
mass isof the neck
hypointense at level
on the of
ADClateral
map cervical
(ADC region,
value of
− 3
shows
0.62 ×2 10high
−3
intensity on DWI; and (c) the mass is hypointense on the ADC map (ADC value of 0.62 × 10 mm /s).
signal intensity
mm /s).
2 on DWI; and (c) the mass is hypointense on the ADC map (ADC value of 0.62 × 10 −3

mm2/s).
One of the considerations that must be taken into account when using diffusion-weighted MRI
One of the considerations that must be taken into account when using diffusion-weighted MRI
forOne
the ofdifferential diagnosis of
the considerations masses is the recognition of the fact using
that some malignant masses
for the differential diagnosis that must be
of masses taken
is the into account
recognition of the when
fact that somediffusion-weighted
malignant masses MRI
behave
forbehave like
the differential a benign tumor
diagnosis independently
of masses is of
the the ‘cut-off’
recognition ADC of value
the obtained
fact that at
somethe end of the study.
malignant masses
like a benign tumor independently of the ‘cut-off’ ADC value obtained at the end of the
These like
behave masses are some primary
a benign or metastatic SCC and‘cut-off’
thyroid ADC carcinoma metastases [3].
at Inthetheend
current
study. These masses tumor
are some independently of the
primary or metastatic SCC and thyroid value obtainedmetastases
carcinoma [3].ofInthe
study, a case with diagnosis of larynx SCC metastasis in the ADC value of 1.20 × 10−3 mm2 /s showed
study. These masses
the current study, aare some
case withprimary
diagnosis or of
metastatic
larynx SCC SCC and thyroid
metastasis in thecarcinoma
ADC value metastases
of 1.20 × [3].10−3In
the feature of a benign tumor. The reason that the high ADC values are non-standardized might be −3
themm /s showed
current
2
study, the feature
a case of a benign
with diagnosis tumor. SCC
of larynx The metastasis
reason that in the ADChigh value
ADC of values
1.20 ×are 10
the presence of small foci of micronecrosis and the hypervascular tumor portions that escalate the
non-standardized might be the presence of small foci of micronecrosis
mm /s showed the feature of a benign tumor. The reason that the high ADC values are
2 and the hypervascular tumor
perfusion effect in some malignant tumors and of dense extracellular fluid in follicular components in
portions that escalate
non-standardized mightthe
beperfusion effectofinsmall
the presence somefoci
malignant tumors andand
of micronecrosis of dense extracellular fluid
the hypervascular tumor
in follicular components in thyroid carcinomas [3]. Considering this situation, the macroscopic
portions that escalate the perfusion effect in some malignant tumors and of dense extracellular fluid solid
in portions
follicularwere determined
components using MRI
in thyroid observations
carcinomas [3]. and the ADC this
Considering measurements were
situation, the made, and the
macroscopic solid
cases with neck masses of thyroid origin were excluded from the study. Although
portions were determined using MRI observations and the ADC measurements were made, and the DW-MRI is more
cases with neck masses of thyroid origin were excluded from the study. Although DW-MRI is more
J. Clin. Med. 2018, 7, 130 8 of 10

thyroid carcinomas [3]. Considering this situation, the macroscopic solid portions were determined
using MRI observations and the ADC measurements were made, and the cases with neck masses
of thyroid origin were excluded from the study. Although DW-MRI is more reliable than that of
J. Clin. Med. 2018, 7, x FOR PEER REVIEW 8 of 10
other MR imaging techniques to identify micronecrosis of primary or metastatic tumors, [18–20] the
differentiation between the viable and necrotic parts of head and neck tumors with DW-MRI by
reliable than that of other MR imaging techniques to identify micronecrosis of primary or metastatic
reconstructing
tumors, [18–20] ADC the maps is possible
differentiation for accurate
between the viablebiopsy results [21].
and necrotic parts In
of addition,
head and neckDW-MRI tumors with
ADC measurement may be used for differentiating residual or recurrent
with DW-MRI by reconstructing ADC maps is possible for accurate biopsy results [21]. In addition, head and neck tumors from
postoperative
DW-MRI with or postradiation
ADC measurement changes may [22].
be used for differentiating residual or recurrent head and
With concern for inaccurate ADC measurements
neck tumors from postoperative or postradiation changes in small
[22]. lesions according to the susceptibility
artifactsWithandconcern
image distortions as a limitation of this imaging
for inaccurate ADC measurements in small lesions technique, neckto
according masses <1 cm in the
the susceptibility
greatest
artifactsminimal
and image transverse diameter
distortions on MRI were
as a limitation excluded
of this imaging from the study.
technique, neck In masses
a study<1bycmChen et al.,
in the
performed to compare
greatest minimal periodically
transverse diameter rotated
on MRI overlapping
were excludedparallel
from lines
the with
study.enhanced
In a studyreconstruction
by Chen et
al., performed
(PROPELLER) DW-MRIto compare
and echo periodically
planar DW-MRI rotatedtechniques,
overlapping it wasparallel lines that
suggested with enhanced
it was possible
to reconstruction
reduce the distortion(PROPELLER) of headDW-MRI
and neckand echo through
masses planar DW-MRI
PROPELLER techniques, it was suggested
diffusion-weighted MRI thatto a
it was
large extentpossible
[23]. to reduce the distortion of head and neck masses through PROPELLER
diffusion-weighted
One of the limitations MRI toof a large extent [23].
the current study was the area of necrosis that showed falsely higher
One of the limitations of the
ADC values, especially in the center of metastatic current study wasneck the area of necrosis
masses that showed
[10]. Therefore, falsely
ADC higher
values were
ADC values, especially in the center
measured by selecting the solid portions of tumors. of metastatic neck masses [10]. Therefore, ADC values were
measured by selecting
In the study, three the solid in
masses portions of tumors.
the benign group indicated lower ADC values than the cut-off
In the study, three masses in the benign group indicated lower ADC values than the cut-off
value in accordance with the malignant mass. In one of these masses, which was tuberculous
value in accordance with the malignant mass. In one of these masses, which was tuberculous
lymphadenopathy (ADC = 0.92 × 10−−33 mm22 /s); restriction of diffusion could be explained by the
lymphadenopathy (ADC = 0.92 × 10 mm /s); restriction of diffusion could be explained by the
presence of inflammatory cells in the pus that reduced the diffusion space of water protons [24].
presence of inflammatory cells in the pus that reduced the diffusion space of water protons [24]. In
In another study, this situation was explained by the thickness of the caseous material of granulomatous
another study, this situation was explained by the thickness of the caseous material of
lesions [25]. Whartin tumor (ADC = 0.88 × 10−3 mm2 /s) was the other case that was falsely diagnosed
granulomatous lesions [25]. Whartin tumor (ADC = 0.88 × 10−3 mm2/s) was the other case that was
as falsely
a malignant
diagnosed tumor as a(Figure
malignant 6). tumor
Intense lymphoid
(Figure accumulation
6). Intense in the stromainand
lymphoid accumulation proliferation
the stroma and
of proliferation
the epithelialofcomponent could be the reason for the limited motion of
the epithelial component could be the reason for the limited motion of the waterthe water protons in the
extracellular
protons in space [3]. Reactive
the extracellular lymphadenitis
space [3]. Reactivewas the third case.
lymphadenitis was A varying
the amount
third case. of fibrosis
A varying amount in the
stroma of inflammatory cells could have resulted in the low ADC value
of fibrosis in the stroma of inflammatory cells could have resulted in the low ADC value by by restriction of the diffusion
of restriction
water molecules [3].
of the diffusion of water molecules [3].

Figure 6. Warthin tumor. (a) Axial T2WI showing the mass localised in the superficial lobe and
Figure 6. Warthin tumor. (a) Axial T2WI showing the mass localised in the superficial lobe and
spreading into the deep lobe of the left parotid gland; (b) the lesion shows high signal intensity on
spreading into the deep lobe of the left parotid gland; (b) the lesion shows high −3signal2 intensity on
DWI; and (c) the lesion is hypointense on the ADC map (ADC value of 0.88 × 10 mm /s) and the
DWI; and (c) the lesion is hypointense on the ADC map (ADC value of 0.88 × 10−3 mm2 /s) and the
tumor was falsely diagnosed as a malignant lesion.
tumor was falsely diagnosed as a malignant lesion.
In the current study, in cases with malignant diseases, the mass appeared hyperintense on
In the current
diffusion study, in atcases
images (obtained with s/mm
b = 1000 malignant
2) and diseases, the mass
with low signal appeared
intensity hyperintense
on ADC maps and,on
diffusion images (obtained 2
conversely, benign massesatappeared
b = 1000 hypointense
s/mm ) andand withhyperintense,
low signal intensity on ADC
respectively. Theremaps
was and,
a
statisticallybenign
conversely, significant difference
masses in ADC
appeared values between
hypointense the malignant masses
and hyperintense, and benign
respectively. lesions
There was a
(p < 0.01). When an ADC value of 1.13 × 10−3 mm2/s or less was used to predict malignancy, the best
results were achieved with high accuracy, with 93.33% sensitivity, 82.35% specificity, 82.35%
positive predictive value, and 93.33% negative predictive value.
J. Clin. Med. 2018, 7, 130 9 of 10

statistically significant difference in ADC values between the malignant masses and benign lesions
(p < 0.01). When an ADC value of 1.13 × 10−3 mm2 /s or less was used to predict malignancy, the best
results were achieved with high accuracy, with 93.33% sensitivity, 82.35% specificity, 82.35% positive
predictive value, and 93.33% negative predictive value.
In this study, the patient groups were heterogeneous with different histopathological entities and
there was a limited number of cases in each benign or malignant group. Further investigations of a
larger series with a specific group of the same pathological diagnosis are necessary.

5. Conclusions
In summary, DW-MRI seems to be a promising non-invasive imaging technique for
characterization of head and neck masses or for any other subjects as discussed above. It can be
concluded that further studies on larger series and advances of diffusion MR techniques to improve
the image quality would help DW-MRI to become a routine imaging technique.

Author Contributions: L.K. conceived and designed the experiments; L.K. and E.K. performed the experiments;
L.K. analyzed the data; L.K. and E.K. contributed reagents/materials/analysis tools; and L.K. wrote the paper.
Acknowledgments: The authors would like to thank Filiz Saçan for help and technical support. The authors
declare that this study has not received any financial support.
Conflicts of Interest: The authors declare no conflict of interest.

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